1z2b

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spinqualitylabelsall models 1z2b, resolution 4.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Tubulin-colchicine-vinblastine: stathmin-like domain complex

Overview

Vinblastine is one of several tubulin-targeting Vinca alkaloids that have, been responsible for many chemotherapeutic successes since their, introduction in the clinic as antitumour drugs. In contrast with the two, other classes of small tubulin-binding molecules (Taxol and colchicine), the binding site of vinblastine is largely unknown and the molecular, mechanism of this drug has remained elusive. Here we report the X-ray, structure of vinblastine bound to tubulin in a complex with the RB3, protein stathmin-like domain (RB3-SLD). Vinblastine introduces a wedge at, the interface of two tubulin molecules and thus interferes with tubulin, assembly. Together with electron microscopical and biochemical data, the, structure explains vinblastine-induced tubulin self-association into, spiral aggregates at the expense of microtubule growth. It also shows that, vinblastine and the amino-terminal part of RB3-SLD binding sites share a, hydrophobic groove on the alpha-tubulin surface that is located at an, intermolecular contact in microtubules. This is an attractive target for, drugs designed to perturb microtubule dynamics by interfacial, interference, for which tubulin seems ideally suited because of its, propensity to self-associate.

About this Structure

1Z2B is a Protein complex structure of sequences from Bos taurus and Rattus norvegicus with MG, GTP, GDP, CN2 and VLB as ligands. Full crystallographic information is available from OCA.

Reference

Structural basis for the regulation of tubulin by vinblastine., Gigant B, Wang C, Ravelli RB, Roussi F, Steinmetz MO, Curmi PA, Sobel A, Knossow M, Nature. 2005 May 26;435(7041):519-22. PMID:15917812

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